Speeches

Vaccines and Immunization for Global Health: The Canadian Story

Arthur J. Carty
BioVision 2005
Lyon, France
12 April 2005

[ PDF Version ]

Opening Remarks

Mesdames et messieurs, messieurs les Prix Nobels, distingué invités, chers collègues et amis. Bonjour. C'est un grand honneur d'être parmi vous pour célébrer aujourd'hui un moment clé d'histoire de la science et des efforts de l'homme pour améliorer la vie et la santé de ses concitoyens.

Permettez-moi d'amorcer cette conférence sur une note historique.

Although the procedure known as variolation - the inoculation of healthy individuals with the excretion from lesions of infected people - was first used in ancient China, Egypt and India to reduce the severity of smallpox, history credits Edward Jenner, a simple country doctor in Gloucestershire, England with the first successful vaccination in 1796 - a defining event in the annals of medicine. Yet it was not until 100 years later that Louis Pasteur and Robert Koch developed the next vaccine. Since then, the impact of vaccination programs in saving countless lives has been so great that the U.S. Centres of Disease Control labelled immunization as the number one medical achievement of the 20th Century.

But one can also argue that the development and success of vaccines, and the Salk Polio vaccine in particular, has had impacts well beyond medicine. Indeed it opened the eyes of the world to the power of science and how fundamental research can result in practical solutions to some of the most difficult challenges faced by humankind. Pasteur himself recognized the connection and said and I quote, "There are no such things as applied sciences only applications of science."

What I would like to do today is to tell you the Canadian story of vaccines: past, present and future, beginning with the Founding of the Connaught Laboratories in 1910.

John G. Fitzgerald and the Founding of Connaught Laboratories

In the summer of 1910, Dr. John Gerald Fitzgerald, a Canadian, worked at the Pasteur Institute in Paris learning how to make rabies, diphtheria and smallpox vaccines and anti-toxins.

In 1913 he returned to the University of Toronto where he prepared the first anti rabies vaccine in Canada. He later proposed to the University that they manufacture and distribute a Canadian-made anti-toxin for diphtheria, a major scourge in those days which killed more than 36,000 Canadian children between 1880 and 1929.

The U of T Anti-Toxin Laboratories were formed in 1914, making the university one of the world's first academic institutions to enter into the commercial production of biomedical products.

With the outbreak of World War I the labs quickly grew into a wartime factory, producing enormous quantities of tetanus- toxoid, anti-typhoid vaccine, diphtheria anti-toxin and anti-meningitis serum, thereby saving the lives of many Canadians who were dying of disease as quickly as they were of war wounds.

In 1917 the Anti-Toxin Labs were renamed the Connaught Laboratories and these played a key role in Canada's first universal immunization against diphtheria in 1926 which essentially eradicated the disease. Success with the diphtheria toxoid led to the introduction of universal immunization against tetanus in 1938 and pertussis or whooping cough in 1943.

In 1972 the University sold the Connaught Labs and they are now a part of the SANOFI-AVENTIS Pharmaceutical empire.

Banting and Best's Discovery of Insulin

No account of Canadian impacts on global health care would be complete without highlighting the work of Frederick Banting and Charles Best in the 1920s. In the summer of 1921 at the University of Toronto they isolated a pancreatic extract which had anti-diabetic characteristics. In 1922 they published results from their first experiments with dogs, entitled "The Internal Secretion of the Pancreas" in the Journal of Laboratory and Clinical Medicine. With help from Professor J.J.R. MacLeod and Bertram Collip, a PhD biochemist, they were able to purify insulin for use on diabetic patients. The first tests conducted early in 1922 had spectacular results. For their work, Banting and McLeod but not, unfortunately, Best, were awarded the Nobel Prize in medicine only 1 year later in 1923, such was the impact of their discovery.

Incidentally, Canada's contribution to insulin research continued with Dr. Saran Narang's pioneering work at the National Research Council in developing a total synthesis of the pro-human insulin gene.

But now back to VACCINES!

The story of the development by Jonas Salk of the Salk Vaccine, building on the monumental work of John Enders at Harvard on tissue culture of the poliomyelitis virus, has been well told. In the United States, there were 58,000 cases of polio in 1954, an epidemic which created polio hysteria and drove the massive and successful field trials of the Salk Vaccine.

Back in Canada, the successful adoption of the Salk Vaccine owes much to the Connaught Labs and scientific leadership and vision of Armand Frappier (a Pasteurian microbiologist) and that of the then Federal Minister of Health, Paul Martin Sr., father of the current Prime Minister of Canada. Paul Martin Senior was himself a victim of polio in early childhood and his son was afflicted too although not as seriously.

I had the privilege and honour of presenting the original correspondence between these two great Canadians to Prime Minister Martin in January of this year following a visit to the Institut Armand Frappier in Laval, Québec.

These personal letters stretching from 1948 to 1956 provide real insights into the dedication and commitment of the Government of Canada and Armand Frappier to medical research - a commitment that continues today.

Let me just quote from two of these letters:

From Paul Martin Senior to Armand Frappier (in September 1954):

" Cher docteur Frappier, . . . Il me fait plaisir d'apprendre que vous avez pu vous mettre en contact avec le Dr Wride (des Laboratoires Connaught) concernant le besoin de préparer de plus grands approvisionnements de vaccins pour combattre la poliomyélite. . . . nous attendions tous avec grand intérêt l'évaluation et les conclusions des expériences américaines . . . "

Et du Dr. Frappier le 26 avril 1955

" Monsieur le Ministre, . . . Vous pouvez être assuré de notre entière collaboration. Nous travaillons jour et nuit à l'augmentation de notre production. Nos nouveaux laboratoires, qui seront terminés en deux mois, nous permettront de préparer toute quantité désirée de vaccin. "

During the year 1955 close to one million children were inoculated in Canada without a single accident through the joint provision of the vaccine by Connaught Laboratories and l'lnstitut de Microbiologie et d'Hygiène (forerunner of l'Institut Armand Frappier).

Today, l'Institut Armand Frappier is a thriving scientific and industrial hub in Canadian Biosciences, housing some 300 researchers and sharing a research park with 70 companies.

Harold Jennings and Meningococcal-C Vaccine

Another highlight of Canada's scientific contributions to vaccine R&D was the development of the Meningococcal conjugate vaccine to treat meningitis. Meningitis has a 10% fatality rate among infected Canadians and many of those who survive are faced with permanent brain damage and deafness. More tragic is the fact that two-thirds of the victims are children under the age of five.

Harold Jennings, a carbohydrate chemist at the National Research Council of Canada, used spectroscopic techniques to determine the structures of the polysaccharides found on the cell surface of the bacteria. This work was instrumental for Emil Gotschlich's research at the Rockefeller University, a co-inventor with Jennings of the first generation group-C meningococcal polysaccharide vaccine.

Jennings' group pioneered the development of synthetic meningococcal vaccines, now known as conjugate vaccines, in the late 1970s. The successful demonstration of the group C conjugate vaccine in 1980 was a genuine breakthrough.

Dr. Francesco Bellini, who was then the CEO of IAF Biochem, which became Biochem Pharma, supported the development and commercialization of this vaccine Neisvac-C. Since its use in a mass vaccination program in the U.K. in 2000, the incidence of group-C meningitis in the UK has diminished by more than 95% and Baxter International is marketing it extensively for use around the world.

The development of conjugate vaccines has proven to be a milestone in vaccine technology, and has saved countless lives to date.

To complete the Canadian universal vaccination story up to recent times, a program of paediatric immunization for measles, mumps and rubella (MMR) was introduced in 1983 essentially eliminating these diseases.

Haemophilus Influenza Type B (Hib) was the leading cause of bacterial meningitis in young children before conjugate vaccination was introduced in 1988. This has largely been eradicated.

Universal immunization against hepatitis B using a surface antigen vaccine was implemented in 1986 and four other vaccines (conjugate pneumococcal, conjugate meningococcal, chicken pox and whooping cough vaccine in adolescence) are currently being implemented by Health Canada as part of the National Immunization Strategy.

Health and Medical Research in Canada today

As outlined above, Canada has a history of excellence in the health sciences field and vaccine development. The government of Canada remains highly committed to public health and medical research so that Canada can continue to contribute to the global health effort. Indeed, good fiscal management has produced eight consecutive years of federal budget surpluses (only country in OECD to do so) and this has allowed Canada to make unprecedented investments in research and development. $13B of incremental funding has been added over the last seven years taking Canadian investments in higher education research per capita to the highest levels in the G7. This is quite an achievement! As examples, the budgets of the federal granting councils have doubled; the Canada Foundation for Innovation was established with a $3.7B endowment for infrastructure; 2000 Canada Research Chairs were set up; and Genome Canada was created with an initial investment of $400M. This has dramatically improved the research environment in our universities to the point where they can compete with the best in the world. The Canadian Institutes of Health Research (CIHR) is Canada's largest funder of health-related research. Its R&D budget has more than doubled from $266 million in 1998/99 to almost $700 million currently - an increase of 150 per cent in just 5 years. Canada has also made substantial equipment and infrastructure investments for health research through the Canada Foundation for Innovation with more than 750 funded projects totalling $672 million since 1998.

The CIHR is investing heavily in research and vaccine development for infectious diseases such as SARS, West Nile Virus and Influenza A and has recently announced a Clinical Research Initiative on vaccines. In addition the Canadian Network for Vaccines and Immunotherapeutics (CANVAC), one of 21 Networks of Centres of Excellence, is dedicated to the search for new vaccines to counter AIDS, cancer and hepatitis C. Another promising initiative, funded by CIHR, CANVAC and the U.S. NIH at the University of Nairobi, led by Dr. Frank Plummer of Health Canada and the University of Manitoba is examining the transition dynamics of HIV in Africa, routes of mother to child transmission and the underlying basis for natural immunity to HIV observed in small groups of highly exposed sex workers.

These investments support leading edge Canadian health-research. The Veterinary Infectious Disease Organization (VIDO) is another example of this world-class effort. VIDO, located at the University of Saskatchewan, is credited with five "world firsts" in animal vaccine research, including the first genetically engineered subunit animal vaccine. VIDO was also the first to demonstrate that DNA immunization, known to lead to a long-lasting and broad spectrum immune response, could be effective in cattle. Lately it has been expanded by the addition of a $62M International Vaccine Centre and bio-containment facility for work on emerging human and animal diseases.

Canada is also investing directly in vaccine development through its Pandemic Influenza Plan, announced in February 2004, which included $24 million to purchase anti-virals. Budget 2005 committed another $34 million over five years to strengthen Canada's pandemic influenza preparedness. The government has a ten year contract with ID Biomedical, a leading Canadian biotechnology firm, to provide capacity to produce 100% of Canada's domestic vaccine needs in the event of an influenza pandemic. To shorten the time between influenza identification and vaccine manufacturing, ID Biomedical has recently announced the development of an experimental vaccine against a strain of the influenza virus H5N1 also known as avian flu.

Medical and health challenges for the future

Despite the remarkable scientific advances in medical science over the past five decades, the incidence and impact of aggressive viral and bacterial diseases is still growing in developing countries that have neither the economic nor scientific resources to address the problems.

Clearly many health issues in the developing world go well beyond scientific research. Sound education, economic development and government health policies and systems are of fundamental importance in this regard. As one example, Canadian efforts are being mobilized around health systems and research for Africa through the unique Global Health Research Initiative - a partnership involving CIDA, Health Canada, IDRC and CIHR.

The scientific communities in the advanced economies, in partnership with countries in Africa, Asia and Latin America, can play a crucial role.

For example, it is now possible to develop a conjugate vaccine to wipe out group-A meningococcal meningitis, the most deadly of the serogroups, particularly devastating in Africa, where it affects thousands of infants and kills hundreds of children each year. This could easily be accomplished by building upon the knowledge pioneered in Canada through the synthesis of the group-C conjugate vaccine.

But because group-A meningitis is almost exclusively a third world problem, it has been difficult to find visionary people and companies to develop and manufacture the necessary vaccine at a price that the third world can afford.

The World Health Organization and the Melinda and Bill Gates Foundation have been actively trying to solve this problem through targeted funding. Canada is doing its best to help, with recent ground breaking legislation to enable the export of lower cost medications to developing countries.

The message I would like to leave with you is that we have come far in our battle against disease but it is far from over. Vaccines are still needed for entrenched diseases such as group B meningitis, tuberculosis, malaria, and AIDS that still plague humanity.

21st century health challenges are global, complex problems that will necessitate a new approach to scientific research. We need to bridge the boundaries between scientific fields, institutions and geographic location to effectively mobilize scarce resources and global expertise. A prime example of this form of collaboration is the International Consortium on Anti-Virals (ICAV) which has evolved from Canada's Protein Engineering Network of Centres of Excellence's (PENCE).

ICAV is a not for profit, large-scale international consortium established to discover and develop new therapeutics that target host functions crucial to the infectivity of many viruses. By linking scientists and practitioners from Universities, Institutes, Hospitals and Industry from around the world, ICAV will facilitate knowledge transfer and accelerate the development and delivery of drugs that target viral diseases worldwide.

Finally, I should mention that in keeping with Canada's Global responsibilities in the health area, our Prime Minister has challenged the Canadian research community through my office, to dedicate at least 5% of Federal R&D expenditures to meet the needs of the developing world. This is a worthy challenge for other countries to match.

Merci beaucoup et bonne chance pour la conférence cette semaine.

Good luck with the rest of the conference.

I would like to acknowledge the help of colleagues at Health Canada and the Public Health Agency for providing me with some of the materials for this talk.